| Autor: |
Villar-Acevedo G; The Department of Chemistry, University of Washington , Box 351700, Seattle, Washington 98195-1700, United States., Lugo-Mas P; The Department of Chemistry, University of Washington , Box 351700, Seattle, Washington 98195-1700, United States., Blakely MN; The Department of Chemistry, University of Washington , Box 351700, Seattle, Washington 98195-1700, United States., Rees JA; The Department of Chemistry, University of Washington , Box 351700, Seattle, Washington 98195-1700, United States., Ganas AS; The Department of Chemistry, University of Washington , Box 351700, Seattle, Washington 98195-1700, United States., Hanada EM; The Department of Chemistry, University of Washington , Box 351700, Seattle, Washington 98195-1700, United States., Kaminsky W; The Department of Chemistry, University of Washington , Box 351700, Seattle, Washington 98195-1700, United States., Kovacs JA; The Department of Chemistry, University of Washington , Box 351700, Seattle, Washington 98195-1700, United States. |
| Abstrakt: |
Cysteinate oxygenation is intimately tied to the function of both cysteine dioxygenases (CDOs) and nitrile hydratases (NHases), and yet the mechanisms by which sulfurs are oxidized by these enzymes are unknown, in part because intermediates have yet to be observed. Herein, we report a five-coordinate bis-thiolate ligated Fe(III) complex, [Fe III (S 2 Me2 N 3 (Pr,Pr))] + (2), that reacts with oxo atom donors (PhIO, IBX-ester, and H 2 O 2 ) to afford a rare example of a singly oxygenated sulfenate, [Fe III (η 2 -S Me2 O)(S Me2 )N 3 (Pr,Pr)] + (5), resembling both a proposed intermediate in the CDO catalytic cycle and the essential NHase Fe-S(O) Cys114 proposed to be intimately involved in nitrile hydrolysis. Comparison of the reactivity of 2 with that of a more electron-rich, crystallographically characterized derivative, [Fe III S 2 Me2 N Me N 2 amide (Pr,Pr)] - (8), shows that oxo atom donor reactivity correlates with the metal ion's ability to bind exogenous ligands. Density functional theory calculations suggest that the mechanism of S-oxygenation does not proceed via direct attack at the thiolate sulfurs; the average spin-density on the thiolate sulfurs is approximately the same for 2 and 8, and Mulliken charges on the sulfurs of 8 are roughly twice those of 2, implying that 8 should be more susceptible to sulfur oxidation. Carboxamide-ligated 8 is shown to be unreactive towards oxo atom donors, in contrast to imine-ligated 2. Azide (N 3 - ) is shown to inhibit sulfur oxidation with 2, and a green intermediate is observed, which then slowly converts to sulfenate-ligated 5. This suggests that the mechanism of sulfur oxidation involves initial coordination of the oxo atom donor to the metal ion. Whether the green intermediate is an oxo atom donor adduct, Fe-O═I-Ph, or an Fe(V)═O remains to be determined. |
